favezelimab/pembrolizumab (MK-4280A)

P2, N=320, Active, not recruiting, Merck Sharp & Dohme LLC | Trial completion date: Nov 2025 --> Jun 2027 | Trial primary completion date: Oct 2025 --> Jun 2026

P3, N=94, Active, not recruiting, Merck Sharp & Dohme LLC | Trial completion date: Nov 2025 --> Feb 2025

P3, N=505, Active, not recruiting, Merck Sharp & Dohme LLC | Trial completion date: Nov 2025 --> Feb 2025

P1/2, N=110, Recruiting, Merck Sharp & Dohme LLC | Active, not recruiting --> Recruiting | N=80 --> 110 | Trial completion date: Nov 2026 --> Nov 2029 | Trial primary completion date: Nov 2026 --> May 2026

P1/2, N=80, Recruiting, Merck Sharp & Dohme LLC | Not yet recruiting --> Recruiting

P3, N=94, Active, not recruiting, Merck Sharp & Dohme LLC | Trial completion date: Jul 2025 --> Nov 2025

P2, N=320, Active, not recruiting, Merck Sharp & Dohme LLC | Recruiting --> Active, not recruiting

P1/2, N=120, Active, not recruiting, Merck Sharp & Dohme LLC | Recruiting --> Active, not recruiting

P1/2, N=80, Not yet recruiting, Merck Sharp & Dohme LLC

P1/2, N=400, Active, not recruiting, Merck Sharp & Dohme LLC | Recruiting --> Active, not recruiting

P1/2, N=80, Active, not recruiting, Merck Sharp & Dohme LLC | Phase classification: P1b/2 --> P1/2

P1, N=482, Completed, Merck Sharp & Dohme LLC | Active, not recruiting --> Completed

P1/2, N=390, Active, not recruiting, Merck Sharp & Dohme LLC | Recruiting --> Active, not recruiting

P3, N=432, Active, not recruiting, Merck Sharp & Dohme LLC | Trial completion date: Nov 2024 --> Nov 2025

P3, N=432, Active, not recruiting, Merck Sharp & Dohme LLC | Trial primary completion date: Feb 2024 --> Aug 2024

P1/2, N=90, Active, not recruiting, Merck Sharp & Dohme LLC | Recruiting --> Active, not recruiting

P1/2, N=370, Active, not recruiting, Merck Sharp & Dohme LLC | Phase classification: P1b/2 --> P1/2

Enrollment is ongoing in Asia, Australia, Europe, North America, and South America. Clinical trial information: NCT02625961.

P1/2, N=400, Recruiting, Merck Sharp & Dohme LLC | Phase classification: P1b/2 --> P1/2

P3, N=360, Recruiting, Merck Sharp & Dohme LLC | Trial primary completion date: Jun 2031 --> May 2027

In addition, patients should also have been ineligible for brentuximab vedotin (BV), relapsed or failed to respond to BV or discontinued BV due to toxicity...Approximately 360 patients will be enrolled and randomly assigned 1:1 to receive coformulated favezelimab 800 mg and pembrolizumab 200 mg intravenously (IV) every 3 weeks (Q3W) or physician's choice of chemotherapy (gemcitabine 800-1200 mg/m2 IV on days 1 and 8 of a 21-day cycle or bendamustine 90-120 mg/m2 IV on days 1 and 2 of either a 21- or 28-day cycle)...Reused with permission. This abstract was accepted and previously presented at the 2023 ASCO Annual Meeting.

With additional follow-up, the combination of favezelimab and pembrolizumab continued to demonstrate sustained antitumor activity and manageable safety in patients with anti–PD-1–naive R/R cHL. Analyses are underway to identify biomarkers predictive of response to the combination of favezelimab and pembrolizumab. Further studies to investigate this combination are warranted.

P1b/2, N=370, Active, not recruiting, Merck Sharp & Dohme LLC | Recruiting --> Active, not recruiting

P2, N=160, Recruiting, Merck Sharp & Dohme LLC | Not yet recruiting --> Recruiting

1 Recent results from MK4280–001 phase I clinical study (NCT02720068) have demonstrated clinical activity of a combined therapy regimen of the anti-LAG3 antibody favezelimab plus pembrolizumab in patients with microsatellite stable metastatic CRC whose tumors express PD-L1 with a Combined Positive Score (CPS) ≥ 1. 4% OA for both endpoints. Conclusions This study demonstrates high external lab reproducibility of PD-L1 IHC 22C3 pharmDx with respect to PD-L1 expression in CRC at the CPS ≥ 1 cutoff.

Here we describe the design and rationale for the open-label, randomized, phase II KEYSTEP-008 trial, which will evaluate the efficacy and safety of pembrolizumab-based combination therapy compared with pembrolizumab monotherapy in chemotherapy-refractory (cohort A) or previously untreated (cohort B) MSI-H/dMMR mCRC. Clinical Trial Registration: NCT04895722 (ClinicalTrials.gov).

Patients were categorized by T-cell-inflamed gene expression profile (TcellGEP) and tumor mutational burden (TMB) status and randomly assigned 1:1:1 to receive pembrolizumab + lenvatinib, pembrolizumab + quavonlimab or pembrolizumab + favezelimab. These data demonstrate the feasibility of prospective TcellGEP and TMB assessment to study the clinical activity of first-line pembrolizumab-based combination therapies in advanced NSCLC. ClinicalTrials.gov registration: NCT03516981 .

P1/2, N=390, Recruiting, Merck Sharp & Dohme LLC | Not yet recruiting --> Recruiting

In this post hoc analysis, the combination of favezelimab + pembrolizumab was associated with a higher ORR and deeper responses than pembrolizumab monotherapy in patients with PD-1–refractory R/R cHL. Although limited by its retrospective nature, the results support the hypothesis that favezelimab contributed substantially to the efficacy observed in the MK-4280-003 study. Clinical trial, Hodgkin's lymphoma, Immunotherapy

Favezelimab + pembrolizumab continued to demonstrate sustained antitumor activity and acceptable safety in anti–PD-1–naive patients with R/R cHL. Further studies comparing this combination with pembrolizumab alone would be beneficial. Clinical trial, Hodgkin's lymphoma, Immunotherapy

The combination of favezelimab plus pembrolizumab continued to demonstrate antitumor activity and manageable safety in pts with R/R cHL whose disease progressed following anti–PD-1 therapy. Clinical trial, Immunotherapy, Hodgkin's lymphoma

P1/2, N=390, Not yet recruiting, Merck Sharp & Dohme LLC

P1/2, N=390, Ongoing, Merck Sharp & Dohme LLC

Favezelimab with or without pembrolizumab had a manageable safety profile, with no treatment-related deaths. Promising antitumor activity was observed with combination therapy, particularly in participants with PD-L1 CPS ≥1 tumors.

After additional follow-up, favezelimab plus pembrolizumab combination therapy continued to demonstrate sustained antitumor activity and acceptable safety in anti–PD-1–naive patients with R/R cHL. Further studies comparing the activity of this combination to that of single-agent pembrolizumab would be of clinical benefit.

After additional follow-up, favezelimab plus pembrolizumab combination therapy continued to demonstrate sustained antitumor activity and acceptable safety in pts with R/R cHL whose disease progressed following anti–PD-1 therapy. A phase 3 study is planned to further investigate the promising results found in this patient population.

The multicohort phase 1/2 MK-4280–003 study (NCT03598608) evaluated the safety and efficacy of a LAG-3 inhibitor favezelimab (MK-4280) + pembrolizumab (pembro) in pts with R/R hematologic malignancies. Favezelimab 800 mg + pembro 200 mg Q3W demonstrated acceptable safety and effective antitumor activity in anti–PD-1–naive pts with R/R cHL. Comparative studies on its activity to that of single-agent pembro would be of clinical benefit.

Favezelimab 800 mg + pembrolizumab 200 mg Q3W demonstrated acceptable safety and effective antitumor activity in pts with R/R cHL and PD following anti–PD-1 therapy. This combination shows potential to reinduce a response in this pt population.

P3, N=360, Ongoing, Merck Sharp & Dohme LLC

P2, N=320, Recruiting, Merck Sharp & Dohme LLC | Trial primary completion date: Sep 2024 --> Sep 2025

Conclusion Favezelimab 800 mg + pembrolizumab 200 mg Q3W demonstrated an acceptable safety profile and effective antitumor activity in anti–PD-1–naïve patients with R/R cHL. Further studies are merited to compare the activity of this combination to that of pembrolizumab alone.

No treatment-related deaths occurred. Conclusion Favezelimab 800 mg + pembrolizumab 200 mg Q3W showed a tolerable safety profile and effective antitumor activity in heavily pretreated patients with R/R cHL whose disease had progressed after anti–PD-1 therapy, suggesting that the combination may reinduce a response in these patients.